In patients with neurological or psychiatric disorders, for example Parkinsonism (Morbus Parkinson), essential tremor, dystony or obsessive disorders, nerve cell groups or networks in circumscribed regions of the brain, for example the thalamus and the basal ganglia, become pathologically active, for example, excessively synchronous in their activity. In this case a large number of neurons generate action potentials synchronously. The neurons involved fire predominantly synchronously. With healthy individuals, by contrast, the neurons in these regions of the brains fire qualitatively differently, for example in an uncontrolled manner.
In the case of Morbus Parkinson, the pathological synchronous activity for example of the thalamus and the basal ganglia, alter the neuronal activity in other grain regions, for example in areas of the cerebral cortex like the primary motor cortex. In that case, the pathological synchronous activity in the region of the thalamus and the basal ganglia has its rhythm impressed upon the cerebral cortex so that the muscles controlled by this region undergo pathological activity, for example, a rhythmic trembling (tremor).
In patients who no longer can be effectively treated by medication, depending upon the pathological patterns and whether the pathology arises from one side or both sides of the brain, a deep electrode can be implanted on one or both sides. A cable runs under the skin from the head to a so-called generator which comprises a control device and a battery and for example can be implanted under the skin in the region of the clavicle. Through the deep electrodes a continuous stimulation is applied with a high frequency periodic pulse sequence (pulse train with a frequency of >100 Hz) of individual pulses, for example rectangular pulses. The goal of this method is to suppress the firing of the neurons in the target regions. The mechanism by which this operates in standard stimulation has not been sufficiently clarified as yet. The results of multiple studies suggest that the standard deep stimulation operates like a reversible leisioning, that is a reversible switch off of the tissue: the standard deep stimulation suppresses the firing of the neurons in the target regions and/or in the brain regions connected therewith.
A disadvantage with this manner of stimulation is that the energy consumption of the generator is very high so that the generator, including its batteries must be replaced by an operative procedure relatively early, after about one to three years. Of even greater drawback is that the high frequency continuous stimulation is unphysiological (unnatural) input in the region of the brain for example the thalamus or the basal ganglia which in a few years can give rise to adaptation of the impacted nerve [c4ell] [cell] networks. In order to produce the same stimulation results, therefore, to overcome this adaptation, higher stimulation amplitudes must be used. The greater the stimulation amplitude, the greater is the probability that as a consequence and stimulation, neighboring areas will be subjected to collateral effects or damage like dysarthria (speech disturbances), dysaesthesis (in part from painful missynesthesia), cerebral ataxy (instability, inability to stand without assistance) or schizophrenic like symptoms, etc. These side effects cannot be tolerated by patients. The treatment, therefore loses its effectiveness in these cases after several years.
As a consequence, another method has been proposed as is described in the German Patent Document DE 102 11766.7 “Device for the Treatment of Patients by Means of Brain Stimulation, An Electronic Unit As Well As The Use of the Device and the Electronic Unit in Medicine”, in which the demand-controlled excitation is applied to, respective target regions in which pathologically synchronized numonal activity is to be desynchronized. The goal of this method/this device is not simply to suppress the pathologically synchronous firing as with standard deep stimulation but to approximate the physiological uncorrelated firing patterns.
In this manner on the one hand the current consumption can be reduced and on the other hand, adaptation processes of the nerve tissue which can require an increase in the stimulation amplitude and give rise to side effects, can be prevented. This demand controlled desynchronization method has however also relevant drawbacks.
Drawbacks of the demand-controlled or need-controlled desynchronization stimulation method of DE 102 117 66.7 results from the following considerations:
In order to desynchronize a synchronized nerve cell network with an electric stimulus, an electrical stimulus of a certain duration must be applied at a certain phase of the pathological rhythmic activity in the target area with precision. Since such a precision cannot be readily determined experimentally at the present time, combinations of stimuli are used. A first stimulus or excitation pulse of such a composite stimulus controls the dynamics of the population to be desynchronized by a reset, that is a new start, while the second excitation of the composite stimulus encounters and desynchronizes the nerve cell group in a vulnerable state it is however unavoidable in this connection, to ensure that the quality of the control, that is the quality of the reset, to provide a stronger stimulus for the reset. This should however be avoided in the sense of minimizing side effects. It is decisive to this end that the desired desynchronizing effect can only arise when the stimulation parameters, thus the duration of the individual excitations and especially the pause between the first and second excitations are optimally selected. This has severe consequences:
1. A time consuming calibration procedure is required which typically lasts longer than 30 minutes
2. As a consequence of the time consuming calibration procedure, the effect of desynchronizing simulation in accordance with DE 102 117 66.7 cannot be made part of an intraoperative selection of the appropriate target point for the insertion of the deep electrode. For that purpose the effect of the desynchronization stimulation according to DE 102 117.66.7 must be tested separately for different target points since for each target point a separate calibration is required. This would decrease the duration of electrode implantation surgery for a patient in a prohibitive manner.
3. With large variations in the network characteristics, that is fluctuations in the parameters which describe the activity of the nerve cell population like, for example, synaptic amplitude and firing rate, new calibrations are required which means that during the calibration, no therapeutic effect can be produced.
4. Since the desynchronizing stimulation according to DE 102 66.7 can only be effective when the frequency of the neuron population to be desynchronized does not have large fluctuations, this stimulation cannot be used with pathologies in which the pathologically excessively synchronized activity arises for only brief periods of time and then with strongly varying frequencies as for example in the case of epilepsy.